Detailed correlative electron-microscopic and histochemical studies will be performed on aneurally cultured human muscle from patients with various neuromuscular disorders and normal persons. The study will aid in the delineation of those features of diseases which are primarily myopathic from those which are secondary, due to influences external to the muscle fiber such as microvascular changes, chemical alterations, immunological mechanisms, and neuronal or axonal dysfunctions. Because knowledge of fundamental changes in diseased human muscles is currently very incomplete, culturing of human muscle in the aneural condition is a technique of choice for investigating the pathogenesis of various neuromuscular disorders. Whether structural (and histochemical) changes present in the patient's biopsied muscle will or will not be reproducible in such an environment could help to elucidate the pathogenesis of a disease. Of the diseases which are reproducible in vitro, we would attempt in vitro "treatment" of some, monitored by electronmicroscopic as well as histochemical and growth parameters; and of some of those which are not, we would attempt to reproduce the disease in human fibers in vitro by manipulations of chemical, immunologic, or other environmental factors of the cultures, also monitored by the same parameters. Ultimately, we will also want to form cross-species neuromuscular junctions on human muscle fibers using embryonic animal motor neurons, monitored by electronmicroscopic, histochemical, and physiologic parameters.